Hereditary sensory and autonomic neuropathy type II

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch to the brain. These sensations are impaired in people with HSAN2. In some affected people, the condition may also cause mild abnormalities of the autonomic neurons, which control involuntary body functions such as heart rate, digestion, and breathing. The sensory and autonomic neurons are part of the body's peripheral nervous system, which comprises the nerves outside the brain and spinal cord. HSAN2 is considered a form of peripheral neuropathy.

The signs and symptoms of HSAN2 typically begin in infancy or early childhood. The first sign of the condition is usually numbness in the hands and feet. Soon after, affected individuals lose the ability to feel pain or sense hot and cold. In people with HSAN2, unnoticed injuries often lead to open sores (ulcers) on the hands and feet. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may require amputation of the affected area. People with HSAN2 often injure themselves unintentionally, typically by biting the tongue, lips, or fingers. These injuries may lead to loss of the affected areas, such as the tip of the tongue. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because of the inability to feel pain. Repeated injury can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are damaged.

The effects of HSAN2 on the autonomic nervous system are more variable. Some infants with HSAN2 have digestive problems such as the backflow of stomach acids into the esophagus (gastroesophageal reflux) or slow eye-blink or gag reflexes. Affected individuals may also have weak deep-tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.

Some people with HSAN2 lose a type of taste bud on the tip of the tongue called lingual fungiform papillae and have a diminished sense of taste.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

There are several types of HSAN2, each caused by mutations in a different gene. HSAN2A is caused by mutations in the WNK1 gene, and HSAN2B is caused by mutations in the RETREG1 gene. Additional types caused by mutations in other genes are rare. Although different genes are involved, all types of HSAN2 have similar signs and symptoms.

The WNK1 gene provides instructions for making multiple versions (isoforms) of the WNK1 protein. HSAN2A is caused by mutations that affect a particular isoform called the WNK1/HSN2 protein. This protein is found in the cells of the nervous system, including sensory neurons. The mutations involved in HSAN2A result in an abnormally short WNK1/HSN2 protein. Although the function of this protein is not well understood, it is likely that the abnormally short version cannot function properly or is broken down. People with HSAN2A have a reduction in the number of sensory neurons; however, the role that WNK1/HSN2 protein changes play in that loss is unclear.

HSAN2B is caused by mutations in the RETREG1 gene. These mutations lead to an abnormally short and nonfunctional protein. The RETREG1 protein is normally found in sensory and autonomic neurons. It is involved in the recycling of worn-out cell parts (autophagy), specifically a cell structure called the endoplasmic reticulum. When the RETREG1 protein is nonfunctional, recycling of the endoplasmic reticulum is impaired. The buildup of these structures likely results in death of the neurons.

The loss of neurons leads to the inability to feel pain, temperature, and touch sensations and to the impairment of the autonomic nervous system seen in people with HSAN2.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

HSAN2 is a rare disease; however, the prevalence is unknown.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal cortical bone morphology · Very frequent (99-80%)

An abnormality of compact bone (also known as cortical bone), which forms the dense surface of bones.

Abnormality of epiphysis morphology · Very frequent (99-80%)

An anomaly of epiphysis, which is the expanded articular end of a long bone that developes from a secondary ossification center, and which during the period of growth is either entirely cartilaginous or is separated from the shaft by a cartilaginous disk.

Abnormality of the ankles · Very frequent (99-80%)

An anomaly of the joint that connects the foot with the leg.

Abnormality of the hip bone · Very frequent (99-80%)

An abnormality of the hip bone.

Abnormality of the knee · Very frequent (99-80%)

An abnormality of the knee joint or surrounding structures.

Dystrophic fingernails · Very frequent (99-80%)

The presence of misshapen or partially destroyed nail plates, often with accumulation of soft, yellow keratin between the dystrophic nail plate and nail bed, resulting in elevation of the nail plate.

Dystrophic toenail · Very frequent (99-80%)

Toenail changes apart from changes of the color of the toenail (nail dyschromia) that involve partial or complete disruption of the various keratinous layers of the nail plate.

Hyperhidrosis · Very frequent (99-80%)

Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.

Other findings in the same source

From: Orphanet

Additional reported features include Hyperlordosis (Very frequent (99-80%)); Osteolysis (Very frequent (99-80%)); Reduced bone mineral density (Very frequent (99-80%)); Skeletal muscle atrophy (Very frequent (99-80%)); Tapered finger (Very frequent (99-80%)); Wormian bones (Very frequent (99-80%)); Acroosteolysis (feet) (Very frequent (99-80%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Hereditary sensory and autonomic neuropathy type II is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.